Abstract

The effect of oxytetracycline (OTC) pretreatment on the response of the ob /ob mouse to insulin secretagogues in vivo and
in vitro was investigated. With glucose loading in vivo, the peak glucose was twofold greater and the insulin levels threefold
greater in obese than in lean mice. After OTC treatment, there was no significant difference in insulin levels between lean
and obese mice although the peak glucose level was still 1.5 times as high. Glucagon increased plasma glucose 2.5-fold and
plasma insulin 20-fold in the obese as compared with lean mice. After OTC treatment, the glycemie response of the obese was
indistinguishable from that of the lean control. The insulin levels, while higher than those of lean mice, were only 25% of
those found in the untreated obese. Aminophylline produced an 8- and a 20-fold increase in peak glucose and insulin levels,
respectively, as compared with lean mice. In the OTC-treated obese mice, the injection of aminophylline produced a slower
rise in plasma glucose than in the obese controls, but the levels were not significantly different from those of the untreated
obese mice at 90 min. On the other hand, the insulin levels attained a plateau at a value which was one-fifth that found in
the control obese group. In vitro, isolated islets from obese mice showed an exaggerated response to the secretagogues. Pretreatment
with OTC attenuated this response. The fraction of insulin released at 10 mM glucose was less than one-fourth that in the
obese controls. With glucagon added, the response was only one-eighth, and with aminophylline, one-half as great in the OTC-treated
than in the obese control. The effects of OTC cannot be attributed to the effects of the drug on food consumption, since obese
mice food restricted to the intake of the OTC-treated obese mice showed either no improvement or much smaller Changes.